The DFCI-based ALL Consortium is a 10-institution childhood ALL clinical trials group that has been conducting multi-institutional studies since 1981. The group has a common treatment philosophy featuring intensive early therapy, and a research focus on doxorubicin, L-asparaginase and central nervous system treatments. The group has demonstrated differences in L-asparaginase dose responses in vivo and in vitro, as well as L- asparaginase species differences in cytotoxicity, pharmacokinetics and pharmacodynamics. Each of those studies was performed on previously untreated leukemia cells. In addition, we have augmented our randomized dose (6-MP) and schedule (doxorubicin) treatment efficacy and toxicity trials by the investigation of the chronopharmacology of those agents. We have also interacted to complete neuropsychological toxicity studies of alternative central nervous system treatments. The group provides over 100 patients per year and enables the clinical and laboratory studies described in the application to be completed.